Thatcherism Plays

Reactive oxygen species (ROS), such as the free radicals (e.g. hydroxyl, superoxide, nitric acid) and certain non-radicals (e.g. lipid peroxide, hydrogen peroxide) lead to damage of specific molecules by a process called oxidative stress, which consequently leads to the injury of the cells or tissues. High level‘s of ROS results from inflammation, viral or fungal infection, ageing, pollution, UV radiation, excessive alcohol consumption, cigarette smoking…etc (Mittler, 2002). The ROSs produced in vivo in respiratory chains of mitochondria, activated polymorpho-nuclear leukocyte, macrophages and peroxisomes. Exogenous sources of these harmful radicals are items such as tobacco smoke, pollutants, pesticides, ionizing radiation and organic solvents (Kumar, 2011).

Neutralization of ROS is accomplished by antioxidants, which are chemicals or substances that retard the damage caused by these free radicals. Well-known antioxidants include enzymes and other substances which are either endogenous (e.g.

superoxide dismutase, catalase, glutathione) or exogenous (e.g. vitamins A, C, E, α-tocopherol, selenium, beta carotene, butylated hydroxyl anisole and butylated hydroxyl toluene) that are capable of counteracting the destructive effects of oxidation. Food products such as vegetable oils and prepared foods are usually supplied with antioxidants to prevent or interrupt their rancidity by the action of air (Halliwell, 1994).

Liver cells, especially hepatocytes, have the excellent ability to metabolize and detoxify ROSs, subsequently repairing damage done by antioxidants. Furthermore, the liver expresses a multi-layered defense system against these ROSs, as it encloses superoxide dismutases (in the cytosol and mitochondria), catalase (in the peroxisomes), glutathione peroxidases (in the cytosol and mitochondria), holds glutathione in its cellular

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compartments besides its cell membranes and carries radical chain-breaking antioxidants like vitamin E. Therefore, ROS could cause instability only on cellular homeostasis, it would lead to cell death if not effectively counteracted (Jaeschke &

Ramachandran, 2011).

Superoxide dismutase (SOD) catalyzes the dismutation of superoxide ion into oxygen and hydrogen peroxide (H2O2). Catalase (CAT) catalyzes the decomposition of hydrogen peroxide to water and oxygen. Glutathione peroxidase (GPX) removes hydrogen peroxide by converting reduced glutathione into oxidized glutathione. These enzymes modulate in several diseases, including multiple sclerosis, alzheimer disease, diabetes, liver cirrhosis and hepatocellular carcinoma (Szymonik-Lesiuk et al., 2003). Previous studies documented a significant decrease in the level of CAT, SOD and GPX enzymes after consequent increase in oxidative stress and free radical levels, resulting in an increase in cellular damage in cirrhotic rats (Abul et al., 2002).

The control of ethanol-induced oxidative stress in alcoholic liver diseases (ALD), hepatic stellate cells (HSC) and inflammatory cells have been shown to initiate the production of hepatocyte growth factor (HGF), which leads to hepatocytes proliferation and repair. HGF has been revealed to decrease ROS production, lipid peroxidation and protein oxidation damage due to ethanol metabolism, with an increase in cell viability.

The mechanism involved in the HGF that induced protection against ethanol toxicity revealed that HGF induces the expression of antioxidant enzymes such as CAT, SOD, and GPX (Gómez-Quiroz et al., 2012).

Liver cirrhosis has been reported to be accompanied by excessive oxidation of polyunsaturated membrane lipids (Poli, 2000). Lipid peroxidation induces over

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expression of fibrotic cytokines, the key molecules in the fibrosis mechanism, as well as increased synthesis of collagen. Thus the hepatic lipid peroxidation has been extensively studied in vitro and in vivo experimental models by measuring malondialdehyde (MDA), a major end product of lipid peroxidation (Poli & Parola, 1997). Lipid peroxidation and subsequently fibrosis have been prevented in the liver of animals supplemented with antioxidants like silymarin (Shaker et al., 2010), Anoectochilus formosanus (Shih et al., 2005), Nigella sativa (Kanter et al., 2003), Rosmarinus officinalis (Gutierrez et al., 2010), Ambrosia maritime (Ahmed & Khater, 2001) and many other plant extracts.

2.3.3.1 Antioxidant properties of medicinal plants

Many synthetic antioxidants e.g. butylated hydroxyl anisole (BHA), butylated hydroxyl toluene (BHT) or tert-butyl hydro quinine (TBHQ) have been restricted against includion in foods because of their toxicity, therefore, attention has been directed towards the improvement of natural antioxidants from plants materials.

Natural antioxidants could be either phenolic compounds (phenolic acid, flavonoid, and tannin), nitrogen containing compounds (chlorophyll derivative, alkaloid, amino acid, amine and peptide,), ascorbic acid, carotenoids or tocopherols and their derivatives.

Thus interest has raisen amongst food manufacturers, scientists and consumers toward‘s antioxidant constituents of botanical sources in the maintenance of health and protection from different diseases and cancer (Dimitrios, 2006).

There have been various in vitro techniques used to determine the effectiveness of plant derived natural antioxidants. These techniques are of two types:

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1) Hydrogen atom transfer reactions, such as total radical trapping antioxidant potential (TRAP), oxygen radical absorbance capacity (ORAC) and β- carotene bleaching.

2) Electron transfer reactions such as ferric reducing antioxidant power (FRAP), trolox equivalent antioxidant capacity (TEAC), α,α-diphenyl-β-picryl-hydrazyl radical scavenging assay (DPPH), hydroxyl radical scavenging assay, superoxide anion radical scavenging assay, total phenolic or flavonoids assays and nitric oxide radical scavenging assay.

However, it is important to apply more than one technique to measure the antioxidant ability of plant extracts because of the complex structure of phytochemicals (Chanda &

Dave, 2009).

Medicinal plants have been screened worldwide for their antioxidant effects. In a study by Adewusi and Steenkamp (Adewusi & Steenkamp, 2011) they reported the antioxidant activities of 12 plants traditionally use in South Africa to treat neurological disorders. Their findings support that the antioxidant activities of plants counteract with the ROS and the cholinesterase mechanisms. In vitro radical scavenging activity of 1,1-diphenyl-2-picrylhydrazyl (DPPH) has been detected with in vivo superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) activities enhanced in Chinese hamster lung fibroblasts (V79-4) treated with methanol extracts of nine medicinal plants traditionally used in Chinese medicine (Lee et al., 2003).

Moreover, correlations were found between the antioxidant activities of 42 plants used traditionally in Thailand and their chemical content such as vitamin C, vitamin E, carotenoids, tannin, and totalphenolics (Chanwitheesuk et al., 2005). Also, the antioxidant capacity and the total phenols and flavonoid contents of kiwi fruit (Actinidia deliciosa) were determined in vitro, by assaying free radical scavenging activities of

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1,1-diphenyl-2-picryl-hydrazyl (DPPH), 2,2′-azino-bis(3-ethyl benzthiazoline-6-sulfonic acid) (ABTS), superoxide anion radical and N,N-dimethyl-p-phenyl enediamine (DMPD), and reducing power of (FRAP) and (CUPRAC) and the metal chelating activities (Bursal & Gulcin, 2011).

The in vitro inhibition of lipid peroxidation, DPPH radical scavenging activity and modulation of mutagenicity in Escherichia coli induced by ter-butyl hydroperoxide (TBH) have been screened in 45 medicinal plants in Cuba (Ramos et al., 2003).

Furthermore, 22 extracts from 14 species of Brazilian medicinal plants were studied for their ability to reduce DPPH free radical and to protect the yeast Saccharomyces cerevisiae cells against the lethal oxidative stress caused by tert-butyl hydroperoxide (TBH) (Silva et al., 2005).

2.3.3.2 Plant-derived polyphenolic compounds

Plant-derived polyphenolic compounds are organic compounds of plant origin with more than one phenol group. Polyphenols are classified by their source of origin, chemical structure and biological function into phenolic acids (benzoic acid and cinnamic acid derivatives), flavonoids (anthocyanins, flavanols, flavones and flavanones) and polyphenolic amides, with some highly polymerised compounds like lignans, melanins and hydrolysable tannins (Tsao, 2010).

Polyphenols are widely involved as the active components in many herbal and traditional medicines. More than 5000 plant polyphenols have been identified and are known to possess a wide range of pharmacological properties (Ullah & Khan, 2008). In recent years, plant-derived polyphenolic compounds were shown to possess a wide range of pharmacological properties, such as anti-inflammatory, antioxidant and DNA

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repair mechanisms (Nichols & Katiyar, 2010). They are recognized as naturally occurring anti-microbial compounds (Taguri et al., 2004) and have been implicated as cancer chemopreventive agents (Stoner & Mukhtar, 1995).

Furthermore, the hepatoprotective effects of different polyphenolic compounds derived from plant origins were reported by (Adzet T, 1987 ; De Oliveira E Silva Am, 2012) and the mechanisms involved in the hepatoprotective effects have been suggested to be related to the inhibition of iron absorption by polyphenol compounds (Mascitelli et al., 2008).